Abstract
Homopolymerization and cluster formation of cellular membrane receptors (MRs) are increasingly recognized as an essential facet of cell signaling and modulator of physiological responses. Yet, there is a lack of tools that can mediate precise stimulation to better understand the mechanisms and effects of clustering. Here, we designed fluorescent semisynthetic nanoparticles (NPs) based on the iron-storage protein ferritin and Staphylococcus aureus protein A to specifically target and activate distinct MRs, without causing side-effects. The NP exhibits high monodispersity and is readily equipped with a variety of antibodies with a K(D) value below 5 nM. Specificity of the NP antigen recognition was evaluated for cells expressing transferrin receptor 1 (TfR1) or the death receptor CD95, both of which displayed NP-mediated cluster formation. Finally, our engineered NP acts as a natural ligand for TfR1 and induces apoptosis signaling solely by CD95 cluster formation in a ligand-independent manner.